The Murchison Widefield Array: Design Overview

The Murchison Widefield Array (MWA) is a dipole-based aperture array synthesis telescope designed to operate in the 80-300 MHz frequency range. It is capable of a wide range of science investigations, but is initially focused on three key science projects. These are detection and characterization of 3-dimensional brightness temperature fluctuations in the 21cm line of neutral hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10, solar imaging and remote sensing of the inner heliosphere via propagation effects on signals from distant background sources,and high-sensitivity exploration of the variable radio sky. The array design features 8192 dual-polarization broad-band active dipoles, arranged into 512 tiles comprising 16 dipoles each. The tiles are quasi-randomly distributed over an aperture 1.5km in diameter, with a small number of outliers extending to 3km. All tile-tile baselines are correlated in custom FPGA-based hardware, yielding a Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point spread function (PSF) quality. The correlated data are calibrated in real time using novel position-dependent self-calibration algorithms. The array is located in the Murchison region of outback Western Australia. This region is characterized by extremely low population density and a superbly radio-quiet environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings of the IEE

Genetic Variants at Chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 Influence the Risk of Breast Cancer in Men

Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleotide polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35) (odds ratio (OR)  = 1.30, p = 7.98×10−4), rs10941679 (5p12) (OR = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2) (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04×10−6). Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs—rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)—showed significant differences in ORs (p<0.05) between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a comparison of the Depression, Anxiety and Stress Scale (DASS) and the hospital, Anxiety and Depression Scale (HADS)

<p>Abstract</p> <p>Background</p> <p>While it is recognised that depression is prevalent in Rheumatoid Arthritis (RA), recent studies have also highlighted significant levels of anxiety in RA patients. This study compared two commonly used scales, the Depression Anxiety and Stress Scale (DASS) and the Hospital Anxiety and Depression Scale (HADS), in relation to their measurement range and cut points to consider the relative prevalence of both constructs, and if prevalence rates may be due to scale-specific case definition.</p> <p>Methods</p> <p>Patients meeting the criteria for RA were recruited in Leeds, UK and Sydney, Australia and asked to complete a survey that included both scales. The data was analysed using the Rasch measurement model.</p> <p>Results</p> <p>A total of 169 RA patients were assessed, with a repeat subsample, resulting in 323 cases for analysis. Both scales met Rasch model expectations. Using the 'possible+probable' cut point from the HADS, 58.3% had neither anxiety nor depression; 13.5% had anxiety only; 6.4% depression only and 21.8% had both 'possible+probable' anxiety and depression. Cut points for depression were comparable across the two scales while a lower cut point for anxiety in the DASS was required to equate prevalence.</p> <p>Conclusions</p> <p>This study provides further support for high prevalence of depression and anxiety in RA. It also shows that while these two scales provide a good indication of possible depression and anxiety, the estimates of prevalence so derived could vary, particularly for anxiety. These findings are discussed in terms of comparisons across studies and selection of scales for clinical use.</p

First spectroscopic imaging observations of the sun at low radio frequencies with the Murchison Widefield Array Prototype

We present the first spectroscopic images of solar radio transients from the prototype for the Murchison Widefield Array, observed on 2010 March 27. Our observations span the instantaneous frequency band 170.9- 201.6 MHz. Though our observing period is characterized as a period of "low" to "medium" activity, one broadband emission feature and numerous short-lived, narrowband, non-thermal emission features are evident. Our data represent a significant advance in low radio frequency solar imaging, enabling us to follow the spatial, spectral, and temporal evolution of events simultaneously and in unprecedented detail. The rich variety of features seen here reaffirms the coronal diagnostic capability of low radio frequency emission and provides an early glimpse of the nature of radio observations that will become available as the next generation of low-frequency radio interferometers come online over the next few years

Scoring of senescence signalling in multiple human tumour gene expression datasets, identification of a correlation between senescence score and drug toxicity in the NCI60 panel and a pro-inflammatory signature correlating with survival advantage in peritoneal mesothelioma

Background: Cellular senescence is a major barrier to tumour progression, though its role in pathogenesis of cancer and other diseases is poorly understood in vivo. Improved understanding of the degree to which latent senescence signalling persists in tumours might identify intervention strategies to provoke "accelerated senescence" responses as a therapeutic outcome. Senescence involves convergence of multiple pathways and requires ongoing dynamic signalling throughout its establishment and maintenance. Recent discovery of several new markers allows for an expression profiling approach to study specific senescence phenotypes in relevant tissue samples. We adopted a "senescence scoring" methodology based on expression profiles of multiple senescence markers to examine the degree to which signals of damage-associated or secretory senescence persist in various human tumours. Results: We first show that scoring captures differential induction of damage or inflammatory pathways in a series of public datasets involving radiotherapy of colon adenocarcinoma, chemotherapy of breast cancer cells, replicative senescence of mesenchymal stem cells, and progression of melanoma. We extended these results to investigate correlations between senescence score and growth inhibition in response to similar to 1500 compounds in the NCI60 panel. Scoring of our own mesenchymal tumour dataset highlighted differential expression of secretory signalling pathways between distinct subgroups of MPNST, liposarcomas and peritoneal mesothelioma. Furthermore, a proinflammatory signature yielded by hierarchical clustering of secretory markers showed prognostic significance in mesothelioma. Conclusions: We find that "senescence scoring" accurately reports senescence signalling in a variety of situations where senescence would be expected to occur and highlights differential expression of damage associated and secretory senescence pathways in a context-dependent manner

Using C. elegans to discover therapeutic compounds for ageing-associated neurodegenerative diseases

Age-associated neurodegenerative disorders such as Alzheimer’s disease are a major public health challenge, due to the demographic increase in the proportion of older individuals in society. However, the relatively few currently approved drugs for these conditions provide only symptomatic relief. A major goal of neurodegeneration research is therefore to identify potential new therapeutic compounds that can slow or even reverse disease progression, either by impacting directly on the neurodegenerative process or by activating endogenous physiological neuroprotective mechanisms that decline with ageing. This requires model systems that can recapitulate key features of human neurodegenerative diseases that are also amenable to compound screening approaches. Mammalian models are very powerful, but are prohibitively expensive for high-throughput drug screens. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for neuroprotective compound screening. Here we describe how C. elegans has been used to model various human ageing-associated neurodegenerative diseases and provide an extensive list of compounds that have therapeutic activity in these worm models and so may have translational potential

Species-specific responses of Late Quaternary megafauna to climate and humans

Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary remain contentious. We use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, underscoring the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.This paper is in the memory of our friend and colleague Dr. Andrei Sher, who was a major contributor of this study. Dr Sher died unexpectedly, but his major contributions to the field of Quaternary science will be remembered and appreciated for many years to come. We are grateful to Dr. Adrian Lister and Dr. Tony Stuart for guides and discussions. Thanks to Tina B. Brandt, Dr. Bryan Hockett and Alice Telka for laboratory help and samples and to L. Malik R. Thrane for his work on the megafauna locality database. Data taken from the Stage 3 project was partly funded by Grant #F/757/A from the Leverhulme Trust, together with a grant from the McDonald Grants and Awards Fund. We acknowledge the Danish National Research Foundation, the Lundbeck Foundation, the Danish Council for Independent Research and the US National Science Foundation for financial suppor

Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes

Background: Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure of enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within the distal intestine. Previous studies that have searched for genes underlying HSCR have focused on ENS-related pathways and genes not fitting the current knowledge have thus often been ignored. We identify and validate novel HSCR genes using whole exome sequencing (WES), burden tests, in silico prediction, unbiased in vivo analyses of the mutated genes in zebrafish, and expression analyses in zebrafish, mouse, and human. Results: We performed de novo mutation (DNM) screening on 24 HSCR trios. We identify 28 DNMs in 21 different genes. Eight of the DNMs we identified occur in RET, the main HSCR gene, and the remaining 20 DNMs reside in genes not reported in the ENS. Knockdown of all 12 genes with missense or loss-of-function DNMs showed that the orthologs of four genes (DENND3, NCLN, NUP98, and TBATA) are indispensable for ENS development in zebrafish, and these results were confirmed by CRISPR knockout. These genes are also expressed in human and mouse gut and/or ENS progenitors. Importantly, the encoded proteins are linked to neuronal processes shared by the central nervous system and the ENS. Conclusions: Our data open new fields of investigation into HSCR pathology and provide novel insights into the development of the ENS. Moreover, the study demonstrates that functional analyses of genes carrying DNMs are warranted to delineate the full genetic architecture of rare complex diseases